Diabetes, the TYK2 Gene and the Interferon Response: In Search for Environmental Causes.
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Type 1 diabetes mellitus (T1DM) is a complex, heterogeneous disease mediated by the interaction of genetic and non-genetic factors. Variants of the HLA-DQA1, HLA-DQB1, HLA-DRB1 genes, which play a critical role in immune responses, account for approximately 40% of the genetic predisposition to the disease. Over 60 additional non-HLA genes are also associated with T1DM (Pociot and Lernmark, 2016), many with defined roles in innate and adaptive immunity (PTPN22, IFIH1, STAT4, CTLA4, etc.), inflammatory responses (IL10, IL21, IL12, IL27, TNFAIP3, PRKCQ, etc.), and apoptosis (BAD, PRKCQ, ERBB3, etc.). Evidence from migrant populations and twin studies also invoke a major causative role for non-genetic factors, most strikingly in adult-onset diabetes. Viral infections (especially by members of the Picornaviridae family) contribute to those non-genetic causes of T1DM (Genoni et al., 2017).
AuthorsToniolo, A; Leslie, RD
- College Publications